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LDK378 (dihydrochloride)

Names

[ CAS No. ]:
1380575-43-8

[ Name ]:
LDK378 (dihydrochloride)

[Synonym ]:
2,4-Pyrimidinediamine, 5-chloro-N-[2-[(1-methylethyl)sulfonyl]phenyl]-N-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-, hydrochloride (1:2)
5-Chloro-N-[2-isopropoxy-5-methyl-4-(4-piperidinyl)phenyl]-N-[2-(isopropylsulfonyl)phenyl]-2,4-pyrimidinediamine dihydrochloride
CS-1407
LDK378 dihydrochloride||LDK-378 dihydrochloride
LDK378 dihydrochloride
W-6134
LDK378 (dihydrochloride)

Biological Activity

[Description]:

Ceritinib dihydrochloride (LDK378 dihydrochloride) is potent inhibitor against ALK with IC50 of 0.2 nM, shows 40- and 35-fold selectivity against IGF-1R and InsR, respectively.

[Related Catalog]:

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> ALK
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> IGF-1R
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Insulin Receptor
Research Areas >> Cancer

[Target]

IC50: 0.2 nM (ALK)[1].


[In Vitro]

Ceritinib (LDK378) shows great anti-proliferative activity in Ba/F3-NPM-ALK and Karpas290 cells with IC50 of 26.0 nM and 22.8 nM, compared with IC50 of 319.5 nM and 2477 nM in Ba/F3-Tel-InsR and Ba/F3-WT cells[1].

[In Vivo]

Ceritinib (LDK378) is designed to reduce the possibility of forming reactive metabolites and shows undetectable levels of glutathione (GSH) adducts (<1%) in liver microsomes. Ceritinib (LDK378) has relatively good metabolic stability, with moderate CYP3A4 (Midazolam substrate) inhibition and hERG inhibition. Ceritinib (LDK378) exhibits low plasma clearance in animals (mouse, rat, dog and monkey) compared to liver blood flow, with the oral bioavailability of above 55% in mouse, rat, dog and monkey. Ceritinib (LDK378) induces a dose-dependent growth inhibition and tumor regression in the Karpas299 and H2228 rat xenograft models, with no body-weight loss. Ceritinib (LDK378) shows no impact on insulin levels or plasma glucose utilization in the mouse upon chronic dosing up to 100 mg/kg[1].

[References]

[1]. Marsilje TH, et al. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013, Jun 6.


[Related Small Molecules]

Insulin(human) | Brigatinib | lorlatinib | Alectinib (CH5424802) | OSI-906(Linsitinib) | Entrectinib | Insulin(cattle) | BMS-754807 | Picropodophyllotoxin | TAE684(NVP-TAE684) | NVP-AEW541 | BMS-536924 | AZD-3463 | NT157 | Repotrectinib

Chemical & Physical Properties

[ Molecular Formula ]:
C28H38Cl3N5O3S

[ Molecular Weight ]:
631.057

[ Exact Mass ]:
629.176086

[ PSA ]:
116.85000

[ LogP ]:
8.87040

[ Storage condition ]:
-20℃

Related Compounds

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